Continuous increase in HIV-1 incidence after the year 2000 among men who have sex with men in Rome: insights from a 25-year retrospective cohort study.

To assess trends in HIV-1 incidence and risk factors for seroconversion among men who have sex with men (MSM) resident in Rome, Italy, a retrospective longitudinal cohort study was conducted over 25 years. Incidence rates and trends were modelled using Poisson regression and risk factors were assessed by multivariate Cox models. Of 1,862 HIV-1-negative individuals, 347 seroconverted during follow-up. HIV-1 incidence rates increased from 5.2/100 persons/year (p/y) in 1986 (95% confidence interval (CI): 2.3­11.5) to 9.2/00 p/y in 1992 (95% CI: 6.4­13.0), decreased to 1.3/100 p/y in 2001 and increased until 2009 (11.7/100 p/y; 95% CI: 7.4­18.6). The risk of HIV-1 seroconversion increased during the study period in younger MSM (incidence rate ratio (IRR) = 17.18; 95% CI: 9.74­30.32 in 16­32 year-olds and IRR = 5.09; 95% CI: 2.92­8.87 in 33­41 year-olds) and in those who acquired syphilis (IRR = 7.71; 95% CI: 5.00­11.88). In contrast, the risk of seroconversion decreased among highly educated MSM (IRR = 0.54; 95% CI: 0.35­0.82) and those without Italian citizenship (IRR = 0.45; 95% CI: 0.28­0.71). The HIV epidemic in MSM living in Rome continues to expand. Targeted prevention programmes against sexually transmitted infections to enhance knowledge transfer and behavioural skills are urgently required.

Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues.

OBJECTIVES: We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor (NNRTI) administered with zidovudine (ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non-TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non-TA group). METHODS: Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non-TA. RESULTS: A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non-TA. No significant differences were observed between the non-TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8-25) vs. 13 (9-32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2-4.9) vs. 4.0 (3.3-4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors (RTIs) occurred at a significant lower frequency in the non-TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non-TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non-TA group (18.5%; P < 0.001). CONCLUSIONS: At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non-TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure.

Effective treatment of Kaposi's sarcoma by electrochemotherapy and intravenous bleomycin administration.

The present prospective study was aimed at evaluating the long-term efficacy of local electrochemotherapy (ECT) with the intravenous administration of bleomycin, on disease progression and viral activity in classic Kaposi's sarcoma (cKS), a vascular tumor related to human herpes virus-8 infection. Eighteen patients affected by isolate or multiple cutaneous lesions, refractory to conventional treatments, although in the absence of visceral involvement, were enrolled in a study. Follow-up visits were performed after 4 weeks and every 6 months for up to 48 months. A more extensive exploration of the immunologic status as well as of virological parameters was performed in nine patients. The results showed a significant clinical improvement in all patients after 4 weeks. A complete regression was observed in 12 patients after the first ECT, while four patients required a second treatment on the residual lesions after 4 weeks from the first intervention. The positive outcome persisted during the subsequent clinical control visits. Two patients, that showed rapidly evolving did not improve and relapsed despite a second round of ECT treatment. Effective treatment was associated with the reduction of viral load to undetectable levels. These data support the conduct of larger studies directed at validating the efficacy of ECT as a first-line therapy for cKS.

No evidence of colonization with community-acquired methicillin-resistant Staphylococcus aureus in HIV-1-infected men who have sex with men.

To assess the prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) colonization in HIV-1-infected men who have sex with men (MSM), a cross-sectional study was conducted on 104 persons attending a large STI/HIV unit in Rome, Italy in the period June 2007-June 2008. Swabs obtained from both anterior nares and S. aureus isolates were characterized by phenotypic and genotypic methods. A total of 24 individuals (23.1%) were colonized with S. aureus but none carried MRSA. No statistically significant association between colonization with S. aureus and behavioural, clinical, virological or immunological characteristics was identified. This study indicates a lack of circulation of CA-MRSA in HIV-1-infected MSM in Italy and underscores large epidemiological differences between the USA and a European country, so that only locally conducted epidemiological studies can provide insight into the local circulation of CA-MRSA in general and selected populations.

CD81 expression on CD19+ peripheral blood lymphocytes is associated with chronic HCV disease and increased risk for HCV infection: a putative role for inflammatory cytokines.

The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-gamma on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV-infected subjects. In addition, the results strongly suggest that the cytokines released by activated lymphocytes at sites of inflammation may play a part in up-regulating CD81 expression.

Crossover versus Stabilometric Platform for the Treatment of Balance Dysfunction in Parkinson's Disease: A Randomized Study.

Balance dysfunctions are a major challenge in the treatment of Parkinson's disease (PD). Previous studies have shown that rehabilitation can play a role in their treatment. In this study, we have compared the efficacy of two different devices for balance training: stabilometric platform and crossover. We have enrolled 60 PD patients randomly assigned to two groups. The first one (stabilometric group) performed a 4-week cycle of balance training, using the stabilometric platform, whereas the second one (crossover group) performed a 4-week cycle of balance training, using the crossover. The outcome measures used were Unified Parkinson's Disease Rating Scale (UPDRS) part II, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Six Minutes Walking Test (6MWT). Results showed that TUG, BBS, and UPDRS II improved in both groups. There was not difference in the efficacy of the two balance treatments. Patients in both groups improved also the meters walked in the 6MWT at the end of rehabilitation, but the improvement was better for patients performing crossover training. Our results show that the crossover and the stabilometric platform have the same effect on balance dysfunction of Parkinsonian patients, while crossover gets better results on the walking capacity.

Behaviour of several 'progression markers' during the HIV-Ab seroconversion period. Comparison with later stages.

Two acute phase reactants, four cytokines, five soluble factors and lymphocyte subpopulations have been simultaneously evaluated in 16 subjects before and closely after the HIV-Ab seroconversion time. The same variables have also been determined in 50 HIV-Ab-negative high risk subjects, in 36 CDC II-III and in 30 CDC IV patients, utilizing a mixed longitudinal epidemiological model. The results show significant variations of few parameters in the early phases (increase: sCD8, beta-2-Microglobulin, sIL-2R, sCD23, Neopterin, IFN-alpha; decrease: CD4+ lymphocytes). In the course of the disease, many others parameters progressively increase (IFN-tau, IL-4, IL-6, acid-alpha 1-glycoprotein, alpha 1-antitrypsin) or decrease (B- and T-lymphocytes). Ferritin, in particular, highly increases only in CDC IV stage. These data may be useful to monitor patients during the entire course of their disease and to suggest the time elapsed from seroconversion.

In vitro adherence of Neisseria gonorrhoeae to human epithelial cells.

Gonococcal adherence was studied in vitro using buccal epithelial cells (BEC). In smears stained with the Gram method, a progressive decrease in gonococcal adherence to the BEC after some culture passages was observed. There was a parallel decrease to almost total disappearance in the number of fimbriated bacteria. An electron microscopy study showed that adherence to the epithelial cells was mediated by fimbriae and, in part, by a polysaccharide component of the bacterial cell wall which seems to guarantee persistent adherence ability, even after the loss of fimbriae.

[Screening for HIV-1 infection targeted to women at a center for sexually transmitted diseases (STD). Comparison between 2 periods of 5 years of work]. / Lo screening per l'infezione da HIV-1 mirato alle donne in un centro per le malattie sessualmente trasmesse (MST). Confronto tra due quinquenni di attività.

OBJECTIVE: To determine changes over time in the proportion of individuals requesting HIV-1 testing represented by women and in the HIV-1 prevalence among women attending a centre for sexually transmitted diseases (STD) in Rome Italy. METHODS: We analysed the computerised clinical records of all women undergoing HIV-1 testing in two five-year periods (i.e., 1985-89 and 1993-97). RESULTS: In the period 1985-89, 2,605 individuals underwent HIV-1 testing; 605 (23.2%) of these individuals were women. In the period 1993-97, 5,981 individuals were tested; 2,015 (33.7%) were women. When analysing the proportion of women tested by exposure category, there was an increase in the proportion of non-drug-using heterosexual women (75.5% in 1985-89 vs. 84.6% in 1993-97) and of women from geographical areas endemic for HIV (1.8% vs. 5.5%, respectively), where as there was a decrease in the proportion of tested women represented by intravenous drug users (12.4% vs. 2.7%). Overall, the prevalence of HIV-1 infection among women decreased (8.8% in 1985-89 vs. 5.0% in 1993-97). When considering specific exposure categories, the prevalence increased among partners of HIV-1 infected males (8.7% vs. 36.5%) and among women from endemic areas (2.8% vs. 9.3%). DISCUSSION AND CONCLUSIONS: The increased proportion of women requesting HIV-1 testing, especially those reporting at-risk heterosexual behaviour, suggests that women are generally more informed with regard to the risks of sexual transmission. However, the increase in HIV-1 prevalence among women with an HIV-1-infected partner and those from endemic areas suggests that programmes for preventing sexual transmission need to be improved.

The lowest X4 Geno2Pheno false-positive rate is associated with greater CD4 depletion in HIV-1 infected patients.

Through this study we evaluated whether the HIV-1 tropism determined by genotypic analysis correlates with HIV-1 markers, such as CD4 cell count and plasma HIV-RNA. The analysis was performed on 1221 HIV-1 B-subtype infected patients with an available V3 sequence (all maraviroc naive). Of them, 532 were antiretroviral therapy (ART) naive and 689 ART experienced. Tropism determination was performed by using the geno2pheno (co-receptor) algorithm set at a false-positive rate (FPR) of 10% and 2%. Potential associations of FPR with CD4 cell count and viraemia were evaluated. Association of V3 mutations with genotypic-determined tropism was also evaluated according to different FPR ranges. About 26% of patients (either ART naive or ART experienced) were infected by X4-tropic viruses (using the classical 10% FPR cut-off). However, a significantly lower proportion of ART-naive patients had FPR ≤ 2% in comparison with ART-experienced patients (4.9% vs. 12.6%, respectively, p <0.001). The risk of advanced HIV-1 infection (with CD4 cell count ≤ 200 cells/mm(3)) was significantly greater in X4-infected patients, either ART-naive (OR (95% CI)), 4.2 (1.8-9.2); p 0.0006) or ART-experienced (2.3 (1.4-3.6); p 0.0003), with FPR set at 2% (but not at 10%). This finding was confirmed by multivariable logistic analysis. No relationship was found between viraemia and FPR ≤2%. Some X4-related mutations were significantly associated with FPR ≤2% (ART-naive patients, S11R, Y21V, G24K and G24R, p ≤0.001; ART-experienced patients, Y7K, S11R, H13Y, p ≤0.002). In conclusion, these findings show that within the context of genotypically-assessed CXCR4 tropism, FPR ≤2% defines (far better than 10%-FPR) a viral population associated with low CD4 rank, with potentially greater cytopathic effect, and with more advanced disease.

Non-B HIV type 1 subtypes among men who have sex with men in Rome, Italy.

An increase in the circulation of HIV-1 non-B subtypes has been observed in recent years in Western European countries. Due to the lack of data on the circulation of HIV-1 non-B subtypes among European HIV-1-infected men who have sex with men (MSM), a biomolecular study was conducted in Rome, Italy. HIV-1 partial pol gene sequences from 111 MSM individuals (76 drug naive and 35 drug experienced) were collected during the years 2004-2006. All these sequences were analyzed using the REGA HIV-1 Subtyping Tool, and aligned using CLUSTAL X followed by manual editing using the Bioedit software. A BLAST search for non-B subtype sequences was also performed. Twenty-six (23.4%) MSM were not Italians. Eight individuals (7.2%) were diagnosed as HIV infected before 1991, 20 (18.0%) between 1991 and 1999, and 83 (74.8%) from 2000 to 2006. Fifteen (15/111, 13.5%) individuals were infected with the non-B subtype. The percentage of infection with HIV-1 non-B subtypes was 8.2% (7/85) among Italian MSM and 30.8% (8/26) among the non-Italians (OR = 4.95 95% IC: 1.40-17.87). Individuals infected with the non-B subtype were significantly younger than those infected with the HIV-1 B subtype (28 years vs. 34 years, p = 0.003). The CRFs were more prevalent (8.1%) than pure subtypes (5.4%), which were distributed as follows: subtype C (2.6%), subtype A1 (1.7%), and subtype F1 (0.9%). Major mutations conferring resistance to antiretroviral drugs (ARV) were not found among HIV-1 non-B subtype drug-naive patients but were found in two ARV-experienced individuals. The data show that viral diversity is likely increasing in a population group that had been previously characterized by the circulation of HIV-1 subtype B.

Parallel conduction of the phase I preventive and therapeutic trials based on the Tat vaccine candidate.

The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 microg, 15 microg or 30 microg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).

Epidemiology of dermatophytoses observed in Rome, Italy, between 1985 and 1993.

Between 1985 and 1993, 13,880 patients were studied for possible forms of dermatophytoses. The most frequently isolated dermatophyte was in 2821 positive cases Microsporum canis (50%), followed by Trichophyton rubrum (27%), Trichophyton mentagrophytes (10.6%), Epidermophyton floccosum (9.3%), Microsporum gypseum (2.3%), Trichophyton violaceum (0.6%), Trichophyton tonsurans (0.2%) and Trichophyton verrucosum (< 0.1%). The genera and species isolated were also considered in relation to the site of the lesion. Our epidemiological data were compared with those obtained by other authors in other cities and with those obtained in Rome in previous studies conducted between 1972-77 and 1978-83. Results obtained by various investigators in Europe are also discussed.

Prevalence of Chlamydia trachomatis in cases of genital non-gonococcal infection according to microbiological and serological investigations.

An investigation on the prevalence of Chlamydia trachomatis was carried out on 231 patients (115 men and 116 women, mean age 31.6 years) with genital non-gonococcal infection in order to study the role of this microorganism in infertility and/or sterility in the Italian population. One hundred and sixty-six apparently healthy subjects (108 men and 50 women, mean age 32.4) were also included as control for serological comparison only. Persons with gonococcal infection were excluded. ELISA method was chosen for the direct C. trachomatis examination of "scraping" samples. Serological investigations were carried out by means of the indirect immunofluorescence test for IgM and IgG determination as well as the immunoperoxidase assay for IgA antibodies. A direct C. trachomatis positive test was demonstrated in 27.8% of men vs. 11.2% in women (p less than 0.01) in the patient group. Anti-C. trachomatis IgG specific antibodies were present respectively at any serum dilution in 50.2% of patients vs. 47.6% of normal subjects respectively (p greater than 0.5). The low presence of C. trachomatis (19.5%) at the direct test contrasts with the higher percentage of anti-C. trachomatis positive patients (50.2%) in the same group suggesting that serological tests may be more useful than the direct test in demonstrating an active C. trachomatis infection provided that IgM, IgG and IgA specific antibodies be contemporaneously investigated.

Prevalence of antibodies to human immunodeficiency virus type 1 and condom use among outpatients at a sexually transmitted disease clinic in Rome.

To assess the prevalence of HIV-1 infection and study selected risk factors among patients attending a clinic for sexually transmitted diseases in Rome, 1442 outpatients seen consecutively between 20 February and 12 December 1989 were anonymously tested for anti-HIV-1. An evaluation of the trend of the HIV-1 infection was attempted by comparing the results of the present study with those obtained from a similar sample studied in 1986 in the same clinic. The overall estimated prevalence of anti-HIV-1 was 1.2% among heterosexual non-drug user subjects and 16.1% among homosexual or bisexual men. The anti-HIV-1 seropositivity was significantly higher in heterosexual subjects who reported sexual contact with intravenous drug users, as compared with those who did not report such exposure (12.5% vs 0.8%, p less than 0.005). Comparing the present data with those of a study conducted in 1986 in the same clinic, a lower prevalence of anti-HIV-1 was found among heterosexual subjects (1.2% in 1989 vs 6.0% in 1986, p less than 0.001). The availability after 1986 of several outpatient facilities attracting seropositive subjects and a change in the sexual behaviour of anti-HIV-1 positive subjects could explain this finding. Twenty percent of the heterosexual subjects and 62% of the homosexual or bisexual men reported consistent use of condoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and determinants of hepatitis C virus infection among individuals at risk of sexually transmitted diseases attending a human immunodeficiency virus type 1 testing program.

BACKGROUND: The role of sexual transmission of hepatitis C virus (HCV) infection is still not completely understood, partly because of the lack of longitudinal studies among cohorts of HCV-negative individuals who engage in at-risk sexual behavior. GOALS: To evaluate the incidence of HCV infection in a population at risk for human immunodeficiency virus type 1 (HIV-1) infection and other sexually transmitted diseases (STD) and to identify factors associated with HCV seroconversion. STUDY DESIGN: A retrospective longitudinal study was carried out on a cohort of consecutive attendees of a voluntary HIV-1 testing and counseling program in a large STD center in Rome. All individuals undergoing at least two consecutive tests for HCV antibodies were enrolled. Clinical data and information on individual behavior were collected for all study participants. RESULTS: Between June, 1992 and December, 1994, a total of 709 individuals (12 intravenous drug users [IDU], 244 homosexuals, and 453 heterosexual non-IDUs), initially negative for HCV antibody, were tested more than once. Among these individuals, 15 HCV seroconversions occurred. The average follow-up time was 1.25 person/years (p/y) for an incidence rate of 1.69 per 100 p/y. The incidence rates by exposure category were 39.30 per 100 p/y among IDUs, 1.37 per 100 p/y among homosexual men, and 0.97 per 100 p/y among heterosexual non-IDUs. Excluding IDUs, of the 697 STD clinic attendees engaging in at-risk sexual behavior, HIV-1-positive status tended to be associated with HCV seroconversion (relative hazard = 5.48; 95% confidence interval = 0.85-35.40). The HCV crude incidence rates among HIV-1-infected patients at enrollment was 11.5%, 4.2%, and 2.4% in those with severe, moderate, and mild levels of immunosuppression, respectively (chi-square for trend = 2.38, P = 0.1). CONCLUSIONS: In this cohort, HCV infection was confirmed to be strongly associated with intravenous drug use. Nonetheless, the occurrence of two thirds of the total HCV seroconversions in non-IDU individuals engaging in at-risk behavior suggests a role of sexual practices in the transmission of the infection. Among non-IDU individuals, the risk for development of HCV infection tended to increase in those who were HIV-1 infected.